Fibroblasts cultured from a patient with the syndrome of leprechaunism (characterized by physical abnormalities, intrauterine growth retardation, and clinical insulin resistance) exhibit abnormalities of insulin receptors, receptors for insulin-like growth factors (IGFs), and impaired stimulation of glucose incorporation by these hormones through these receptors. In our studies of the insulin-like growth factor (somatomedin) multiplication stimulating activity (MSA), a polypeptide synthesized by a cloned line of rat liver cells (BRL 3A), progress has been made in the following areas: (i) demonstration of a biosynthetic precursor of MSA (presumably pre-pro-MSA) in a cell-free translation system and of pro-MSA in intact cells; (ii) demonstration by affinity crosslinking of two IGF receptor subtypes that differ in reactivity with insulin, IGF-I and IGF-II, and in subunit structure; (iii) purification of the rat chondrosarcoma IGF-II receptor; (iv) demonstration that MSA is the major somatomedin in fetal rat serum and rat embryo fibroblasts, that it is positively regulated by ovine placental lactogen, and that MSA levels fall shortly after birth; and (v) characterization of growth hormone-dependent binding proteins for somatomedins in human serum and fetal and postnatal rat serum.